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Background: Morphine is widely used to treat moderate-to-severe cancer pain. However, it causes various adverse effects, with morphine-induced fever being an extremely rare and poorly understood symptom., Case Presentation: We report the case of a 58-year-old Chinese woman with advanced lung cancer. Due to the ineffectiveness of tramadol for pain relief, her treatment regimen was switched to morphine. Following the change, she developed nausea, vomiting, dizziness, and elevated body temperature. A similar episode occurred subsequently. After a drug review, the pharmacist speculated that morphine was the most likely causative agent. Upon discontinuation of morphine, her body temperature returned to baseline levels., Conclusions: This case highlights the need for healthcare providers to consider morphine as a potential cause of unexplained fever in patients. The fever may be caused by a hypersensitive response, as there was a significant increase in eosinophils during the fever episodes., (© 2024. The Author(s).)

Competing Interests: The authors have no conflicts of interest to declare.

Objective Drug fever is defined as a fever that temporally coincides with the start of a culprit drug and disappears after discontinuation of the drug. It is a common cause of nosocomial fever, which refers to a fever that develops beyond the first 48 h after hospital admission. However, the exact prevalence of drug fever among cases of nosocomial fever is unclear, as is the variation in prevalence depending on the clinical setting and most common causative drugs. Methods PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were systematically searched. Studies that reported the prevalence of drug fever in patients with nosocomial fever were included. Two of the four reviewers conducted independent assessments of the inclusion, data extraction, and quality. Pooled adjusted odds ratios were generated using a random-effects model and presented with 95% confidence intervals (CIs). Results Fifteen meta-analysis from 15 studies were included. Ten studies did not report the definition of drug fever or excluded febrile patients who were admitted to the hospital within 24-48 h. The pooled prevalence of drug fever among cases of nosocomial fever was 3.0% (95% CI, 0.6-6.8%), which was largely consistent across the settings, except for at oriental medicine hospital. Only four studies reported the causative agents, and antibiotics were the most frequently reported. Conclusions The prevalence of drug fever is low in patients with nosocomial fever. Clinicians should recognize that drug fever is a diagnosis of exclusion, even in cases of nosocomial fever.

Patients infected with COVID-19 can develop coinfections or acute respiratory disorder that result in ventilation. Dexmedetomidine is a common medication used to sedate ventilated patients in the intensive care unit and for nonintubated patients prior to a surgical procedure. As a highly selective alpha-2 agonist, dexmedetomidine provides sedation while reducing the need for anxiolytics or opioids. However, previous case reports suggest dexmedetomidine can induce fever in a variety of conditions. The purpose of this case report is to describe a patient who acquired a fever of 42.6°C in the setting of COVID-19 after administration of dexmedetomidine., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Previous studies have reported low incidence of carboplatin-related drug fever in early cancer treatment cycles. This study describes and analyzes relatively higher incidence rate of carboplatin-related drug fever associated with gynecologic cancer chemotherapy in order to allay anxiety in patients and avoid unnecessary interventions., Materials and Methods: All gynecologic cancer cases treated with carboplatin in a women's hospital in 2017 and 2018 were retrospectively reviewed and analyzed. Data for patients who experienced carboplatin-induced drug fever and those who received the same treatment but did not experience drug fever were compared for statistical significance. Risk factors for drug fever were identified by logistic regression analysis., Results: In total, 318 females with a mean age of 52 years were included in the analysis. Drug fever was observed in 25 patients (7.86%) in 45 cycles of total 1605 carboplatin-containing infusions. Fever occurred at a median of the third (range: 1-7) cycle, starting at 10.62 h (range: 1.18-50.35 h) after carboplatin infusion, and was generally controlled within 3 days. After chemotherapy rechallenge, the mean frequency of drug fever was 2 times per patient (range: 1-4 times). There were 35/45 drug fever incidents (77.78%) that were classified as grade II; in 15/45 cases (33.33%), antibiotic treatment was immediately initiated to prevent infection. Younger age was found to be a risk factor for drug fever following carboplatin treatment (odds ratio = 0.126, 95% confidence interval: 0.025-0.628; p < 0.05)., Conclusions: The retrospective analysis demonstrated that carboplatin-induced drug fever, which occurred on post treatment 3 days, was a type of delayed hypersensitivity reaction with an incidence rate of 7.86% in gynecologic cancer. Younger age was identified as a risk factor. Drug fever is generally tolerated by patients, who insist on chemotherapy. Knowledge of carboplatin-induced drug fever may help physicians reach timely recognition for appropriate interventions., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

Favipiravir, an antiviral agent, is undergoing clinical trials for treating novel coronavirus disease 2019 (COVID-19). Here, we report two cases of COVID-19 with favipiravir-induced fever. In both cases, pyrexia was observed following the administration of favipiravir despite improvements in symptoms of COVID-19. No other cause for fever was evident after careful physical examination and laboratory investigation. The fever subsided in both patients after the discontinuation of favipiravir. To the best of our knowledge, this is the first report of favipiravir-induced fever in COVID-19 patients., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We herein report the first case of a fever induced by favipiravir, a potential coronavirus disease 2019 therapeutic drug. An 82-year-old man diagnosed with bilateral pneumonia was transferred to our hospital following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test. He was treated with compassionate use of favipiravir. Both his oxygen demand and fever gradually improved after admission; however, his fever relapsed, and the C-reactive protein (CRP) levels increased on day 7. We diagnosed his fever as being favipiravir-induced. The fever resolved a few days after favipiravir discontinuation, demonstrating the accuracy of the diagnosis. This case revealed that favipiravir can induce a fever.

Background: Few studies have characterized the clinical manifestations of delayed antibiotic hypersensitivity (AH) diagnosed using objective methods. The lymphocyte transformation test (LTT) is a reproducible method to diagnose type IV hypersensitivity. The purpose of the study was to evaluate the characteristics of delayed AH diagnosed on LTT in children., Methods: We performed a retrospective analysis of patients who were evaluated for AH using LTT at National Center for Child Health and Development, Tokyo, from 2002 to 2014. We extracted patient demographics, type and duration of antibiotics, and clinical characteristics from the medical records. Clinical manifestations were compared between LTT-positive and LTT-negative cases., Results: Seventy-five cases for which 101 drugs were tested were included in this study. LTT was positive against 34 drugs in 26 cases. Median age was 5 years (IQR, 1-9 years), and 49% of patients had underlying disease. LTT was performed at a median of 18 days (IQR, 4-59 days) after the suspected episode. The median number of days from the initiation of therapy to the onset of symptoms was 4. Rash was the most common manifestation (89%). Fever (>38°C) was observed in 20 cases (27%). Onset of fever preceded the rash in nine cases (45%), appeared simultaneously in five (25%), appeared afterwards in four (20%), and was unknown in two (10%). Fever was an independent factor associated with AH when comparing LTT-positive and LTT-negative cases (OR, 3.61; 95%CI: 1.03-12.64)., Conclusions: Fever was a common presenting symptom of delayed AH in children aged ≤18 years., (© 2019 Japan Pediatric Society.)

Enoxaparin (clexane) is a low-molecular-weight heparin commonly prescribed for the chemoprophylaxis of venous thromboembolism in postoperative hip or knee replacement or abdominal surgery patients. We herein report a case of persistent postoperative fever in a patient, likely due to enoxaparin use. Prompt resolution of the patient's fever was observed after discontinuation of subcutaneous enoxaparin for chemical thromboprophylaxis. Reliable incidence data are lacking. A comprehensive search of PubMed, MEDLINE and EMBASE databases, as well as grey literature, found only two prior single case reports on enoxaparin-related fever. The mechanism responsible for the febrile reaction is likely an idiosyncratic response. Enoxaparin is typically derived from bovine or porcine intestines and lungs, hence its potential to cause hypersensitivity reactions is perhaps unsurprising. Clinicians should be alert to this possibility., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Drug fever is a febrile reaction induced by a drug without additional clinical symptoms. This adverse reaction is not rare but under diagnosed and under reported. Doxycycline is a tetracycline compound with broad-spectrum antibiotic activity. Drug fever induced by doxycycline is rarely reported. In this study, we describe a patient in whom doxycycline induced drug fever after 17 days of therapy for brucellosis.

Background and Aims: Tuberculosis is a major global health problem. However, anti-tuberculosis drug treatment has many adverse effects, such as drug-caused fever. The aim of this study was to investigate the clinical features and treatments of anti-tuberculosis drugs-induced fever., Methods: A total of 78 inpatients and outpatients with pulmonary tuberculosis accompanied by drug fever during the anti-tuberculosis treatment were analysed retrospectively from April 2006 to March 2013., Results: Among the anti-tuberculosis drugs that caused the drug fever, rifampicin was the most common one, followed by para-aminosalicylic and pyrazinamide. The symptoms occurred within 2 months after treatment, mainly in the 1-3 weeks, and the main symptom was high fever with body temperature above 39°C. The accompanying symptoms include rash, chills, headache, stuffy nose, runny nose, nausea, vomiting and joint pain. Routine blood examination found that eosinophilia increased in 15 cases and decreased in another 15. Among 63 patients who underwent liver function tests, there were 10 cases of abnormal function and 4 cases of liver damage. When the drug fever was suspected, the measure of withdrawal was taken first. All the suspected drugs were withdrawn in 59 cases, while gradual withdrawal was conducted in 19 cases. Patients with complications were first treated in accordance with the principles of complications treatment and then were gradually given some drugs after recovery. The patients without complications were gradually given some drugs after the body temperature was back to normal., Conclusion: Drug fever is an allergic reaction, the resolution of which depends on whether it was accompanied by liver damage and/or rash or not., (© 2014 John Wiley & Sons Ltd.)

Background: This study was undertaken to analyze the characteristics of fever after cancer chemotherapy in order to reduce unnecessary medical care., Methods: Retrospectively, 1016 consecutive cycles of cancer chemotherapy were analyzed. Fever was defined as a temperature of ≥ 37.5 °C lasting for 1 h. Age, sex, tumor histology, the treatment regimen, the timing of fever onset, the number of days for which the fever persisted, the cause of the fever, the presence or absence of radiotherapy, and the use of granulocyte colony-stimulating factor (G-CSF) were examined., Results: The patients included 748 males and 268 females (median age = 68, range = 29-88), of whom 949, 52, and 15 were suffering from lung cancer, malignant pleural mesothelioma, and other diseases, respectively. Fever was observed in 367 cycles (36 %), including 280 cycles (37 %) involving males and 87 cycles (32 %) involving females. Fever occurred most commonly in the first cycles and was higher than later cycles (41 vs. 30 %, p < 0.001). Fever occurred most frequently on posttreatment days 4 (8 %), 3 (7 %), and 12 (7 %), and the distribution of fever episodes exhibited two peaks on posttreatment days 3 and 4 and 10-14. Fever on posttreatment days 3 and 4 was most commonly observed in patients treated with gemcitabine (20 %) or docetaxel (18 %). The causes of fever included infection (47 %; including febrile neutropenia [24 %]), adverse drug effects (24 %), unknown causes (19 %), and tumors (7 %). Radiotherapy led to a significant increase in the frequency of fever (46 vs. 34 %, p < 0.001). Thirty-three percent of patients received G-CSF, and the incidence ratios of fever in patients who received G-CSF were higher than those who did not receive G-CSF (44 vs. 31 %, p < 0.001)., Conclusion: The febrile episodes that occurred on posttreatment days 3 and 4 were considered to represent adverse drug reactions after cancer chemotherapy. Physicians should be aware of this feature of chemotherapy-associated fever and avoid unnecessary examination and treatments including prescribing antibiotics.

We present a case of a 63-year old man with severe chronic plaque psoriasis and a recent history of lung cancer, wherein fever appeared suddenly after initiation of treatment with low dose acitretin. Tumor recurrence or infection was not found during extensive examinations, nevertheless the patient was empirically treated with broad-spectrum antibiotics without any effect on fever. Immediately after discontinuation of acitretin therapy, the fever disappeared. The patient was followed for next 2 years, during this period similar problems did not reappear, although there has been a relapse of psoriasis and the patient was switched later on biological treatment., (© 2015 Wiley Periodicals, Inc.)

Few studies have reported that fever is caused by intravenous sedative drugs even though these agents are widely used. We present a case of propofol-induced drug fever. A 57-year-old woman underwent hepatic segmentectomy. Although she was diagnosed with type I glycogen storage disease when in her twenties, her liver function was normal. As the operative hemorrhage was high, the patient was transferred to the intensive care unit (ICU). Her temperature at ICU admission was 35.8 °C, and sedation with propofol and dexmedetomidine was initiated. Two hours after admission to the ICU, the patient had a fever of 38-39.5 °C. Remittent fever persisted until day 5 after surgery. Because of her persistent fever, pneumonia was suspected and antibiotics were initiated on day 4 after surgery. As the fever persisted after the initiation of antibiotics, drug fever was suspected. On day 5 after surgery, propofol infusion was discontinued and the patient was extubated. Her temperature of 37.7 °C at the discontinuation of propofol infusion, and rapidly decreased to 36.1 °C in the following 3 h. Propofol-induced drug fever must be considered in cases of fever of unknown origin when patients receive propofol and appear inappropriately well for the degree of fever that they have.

Purpose: Hydroxyurea (HU) or hydroxycarbamide is an antimetabolite chemotherapy frequently used in the treatment of chronic myeloproliferative disorders. This treatment is usually well tolerated but a few cases of fever induced by the molecule have been reported in the literature. The aim of the study was to describe the clinical and biological characteristics of HU induced fever., Methods: We performed a cross sectional study of patients treated with HU and followed-up in an internal medicine department between 2006 and 2012. We added our cases of HU induced fever with those reported in the literature (Pubmed and Cochrane databases) since 1981., Results: We identified 38 cases of HU induced fever, including our 4 cases. The mean age was 65±10.9 years and the sex-ratio 1/2. The fever appeared after a median duration of treatment of 21 days and was usually high (40°C) but clinically well tolerated. A biological inflammatory syndrome (CRP: 131±92 mg/L) was constant and one third of the patients also presented with hepatitis or lung disease. A probabilistic antibiotic treatment was introduced for 34% of the patients. For the half of the patients, HU-reintroduction test was performed, and was positive for all the patients but one. As soon as HU was withdrawn, the fever disappeared in a median of 24 hours., Conclusion: HU induced fever is unusual. Clinical presentation is very stereotyped. When this adverse effect is suspected, an infectious disease must first be ruled out. If infection is excluded, HU has to be stopped., (Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Drug fever (DF) is a febrile reaction induced by a drug without additional clinical features like skin eruption. This adverse drug reaction is probably common but under diagnosed. While its outcome is generally favourable, DF generates unnecessary diagnostic procedures as well as hospitalisations or hospitalisation prolongations. Clinical presentation and biological findings are not specific. Fever is generally well tolerated but may be accompanied by general symptoms mimicking sepsis. Moderate biological disorders could be expected, including elevation or decrease in white blood cell count, eosinophilia, liver cytolysis, and increased C-reactive protein. An infection should be systematically ruled out. Clinical or biological signs of severity should question DF diagnosis. When DF is suspected, the involved drug(s) should be stopped after a reliable assessment of imputability. Antibiotics represent the most often implicated drugs. Fever disappearance after discontinuing the suspected drug is the cornerstone of DF diagnosis. Before stopping the administration of the suspected drug(s), a risk/benefit ratio assessment is necessary. Consistently, it may be complicated to stop an antimicrobial drug when treating an infection or an immunosuppressive drug if required., (Copyright © 2013. Published by Elsevier SAS.)

Underdiagnosis of drug-induced fever leads to extensive investigation and prolongation of hospitalization, and may lead to multiple unnecessary invasive procedures and a wrong diagnosis. Azathioprine is a widely used immunosuppressive drug. We report a case of a 53-year-old female patient diagnosed with autoimmune hepatitis treated with azathioprine, who presented to the emergency room with a 6-wk history of fever and chills without other associated symptoms. Since the patient's fever was of unknown origin, she was hospitalized. All treatment was stopped and an extensive workup to explore the source of fever and chills was performed. Results of chest X-ray, viral, urine, and blood cultures, autoimmune serology, transthoracic and transesophageal echocardiography, and abdominal ultrasound revealed no source of infection. A rechallenge test of azathioprine was performed and the fever and chills returned within a few hours. Azathioprine was established as the definite cause following rechallenge. Fever as an adverse drug reaction is often unrecognized. Azathioprine has been reported to cause drug-induced fever in patients with inflammatory bowel disease, rheumatoid arthritis, and sarcoidosis. To the best of our knowledge there have been no previous reports documenting azathioprine-induced fever in patients with autoimmune hepatitis. The occurrence of fever following the readministration of azathioprine suggests the diagnosis of drug-induced fever, particularly after the exclusion of other causes. A careful rechallenge is recommended to confirm the diagnosis.

Brucellosis, a zoonotic ailment induced by the Brucella and some patients may present with joint involvement. This report describes a pediatric patient diagnosed with Brucella arthritis, presenting with swelling and pain in the right knee. The patient had a reoccurrence of fever due to sulfamethoxazole-trimethoprim allergy during treatment. Symptoms improved after adjusting the antimicrobial regimen to ceftriaxone and rifampicin. This case emphasizes the importance of the need for brucellosis as a differential diagnosis for arthralgia and fever in brucellosis- endemic areas. Furthermore, it emphasizes the importance of timely recognition that recurrent fever after effective anti-infective therapy must be considered as a possibility of drug fever. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infection (PJI) after total knee arthroplasty remains a challenging complication. The treatment options for PJI include different procedures; however, regardless of the strategy, antibiotics are required. The combination of different antibiotics increased the rates of PJI eradication. For almost 3 decades, rifampicin has been used as part of antibiotic therapy for PJI. Drug fever, a febrile response that coincides with the onset of drug administration and disappears after drug discontinuation in the absence of other underlying conditions that could cause fever, is frequently misdiagnosed. We present the case of a 72‐year‐old man with PJI 6 months after total knee arthroplasty. Two‐stage revision surgery was followed by culture‐directed antibiotic treatment (ciprofloxacin and rifampicin) against Staphylococcus aureus isolated from the periprosthetic tissue. On the fifth day of antibiotic treatment, the patient became febrile and, in the next 5 days, he had an intermittent fever of up to 40°C, although he showed clinical improvement. The patient was normotensive without a maculopapular rash, urticaria or clotting abnormalities. A drug fever was suspected, and rifampicin was discontinued. A re‐challenge test was performed, and the fever recurred. Antibiotic treatment with ciprofloxacin was continued and, after 12 months of follow‐up, the patient was doing well. Clinicians should be aware that fever could be a clinical presentation of drug fever. If it occurs during an infection, drug fever could necessitate additional diagnostic procedures for further evaluation, inadequate antibiotic therapy and prolonged hospitalisation. [ABSTRACT FROM AUTHOR]

Summary: What is known and objective: Drug fever is frequently misdiagnosed, especially during concurrent infection. Celecoxib causes various adverse effects; however, celecoxib‐induced drug fever is rarely reported. Case summary: A 32‐year‐old man presented with pyrexia after 17 days of celecoxib therapy, which was reintroduced following 3‐day total drug cessation. His fever recurred after this unsuspected rechallenge, which aided in the ultimate identification of the offending drug. A Naranjo Score of 8 led us to infer that drug fever was "probably" caused by celecoxib. What is new and conclusion: This is the first report of celecoxib‐induced drug fever, aimed at assisting its diagnosis, particularly with rarely suspected causative drugs. [ABSTRACT FROM AUTHOR]

Patient admitted to intensive care units frequently have fevers. A less common cause for fever is a drug-induced fever. For patients who are candidates for heart transplantation, persistent fevers can place a hold on their transplant candidacy until the etiology is found and the fevers resolve. We present a case of a patient with dilated cardiomyopathy who experienced fevers thought secondary to heparin that improved only with discontinuation of therapy and later underwent successful heart transplantation. Only three prior case reports of heparin-induced fevers are currently described in literature. [ABSTRACT FROM AUTHOR]

Fever is considered a protective response having multitude of benefits in terms of enhancing resistance to infection, recruiting cytokines to the injured tissue, and promoting healing. In terms of an injured brain, this becomes a double-edged sword triggering an inflammatory cascade resulting in secondary brain injury. It is important to identify the etiology so that corrective measures can be taken. Here we report a case of persistent fever in a patient with Guillain-Barré syndrome, which was probably due to heparin. This is the first report of heparin-induced fever in a neurocritical care setting and third report overall. [ABSTRACT FROM AUTHOR]

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The article offers an overview of case reports. One case focuses on the probable interaction between the oral anticoagulant warfarin and menthol cough drops in an African-American man. Another case concerns with the link between the drug vardenafil and sudden sensorineural hearing loss in a patient with erectile dysfunction. Another one involves fever induced by the antimetabolite mercaptopurine in an acute lymphoblastic leukemia patient.

Drug fever is a common condition that is frequently misdiagnosed. It is a febrile response that coincides temporally with the administration of a drug and disappears after discontinuation of the offending agent. Drug fever is usually suspected when no other cause for the fever can be elucidated, sometimes after antimicrobial therapy has already been started. In nonsensitized individuals receiving a drug for the first time, the onset of fever is highly variable and differs among drug classes, but most commonly appears after 7-10 days of drug administration and rapidly reverses after discontinuation of the drug. Early diagnosis may reduce inappropriate and potentially harmful and expensive diagnostic and therapeutic interventions. Rechallenge with the offending agent will usually cause recurrence of fever within a few hours, confirming the diagnosis. Rechallenge is controversial and should be performed with extreme caution, since there is a potential for a more severe drug reaction. We describe the mechanisms in the pathophysiology of drug fever and summarize the results of published case reports on the wide variety of agents that are implicated in causing drug fever. Special attention is paid to the role of antimicrobial agents in drug fever. [ABSTRACT FROM AUTHOR]

Introduction: A variety of medications may cause drug fever. Drug fevers may persist for days to weeks until diagnosis is considered. The diagnosis of drug fever is confirmed when there is resolution of fever within 3 days after the medication is discontinued. Only rarely do undiagnosed drug fevers persist for over 3 weeks to meet fever of unknown origin (FUO) criteria. FUOs due to drug fever are uncommon, and drug fevers due to immunosuppressive drugs are very rare. Case report: This is a case of a 58-year-old female renal transplant recipient who presented with FUO that remained undiagnosed for over 8 weeks. Discussion: We believe this is the first reported case of an FUO due to drug fever from sirolimus in a renal transplant recipient. [ABSTRACT FROM AUTHOR]

The occurrence of fever and the clinical profile of febrile patients on the medical service of a teaching hospital were studied prospectively. Thirty-six per cent of 972 patients developed fever (temperature exceeding 38°C). Their 13% mortality rate and 13.2-day average hospital stay exceeded the 3% mortality and seven-day hospitalization for afebrile patients (p<0.0001 for both). Most fever episodes occurred during the first two hospital days. Approximately 30% of first and subsequent fever episodes were caused by bacterial infections; illnesses involving tissue necrosis (e.g., stroke, myocardial infarction) accounted for 20%. Five conditions comprised 53% of diagnoses: respiratory and urinary tract infections, neoplasm, myocardial infarction, and drug reaction. Only one patient had a fever of uncertain origin. Several clinical clues used frequently to identify bacterial infections were reevaluated. Patients with bacterial infections had higher temperatures on the first febrile day (mean 38.9°C) and were more likely to have had prior infections than those with other causes of fever (mean 38.3°C, p<0.001). Older patients (>75 years) had a lower febrile response to bacterial infections than younger patients. Fever in hospitalized medical patients is a common and important concomitant of increased mortality and length of hospitalization. [ABSTRACT FROM AUTHOR]

Burn patients are often plagued by fever due to the inflammatory nature of their injuries as well as the normal postoperative systemic inflammatory response syndrome. One etiology for fever, often not initially considered, is drug-induced fever. A rare cause of drug-induced fever is heparin with only one documented case reported in the literature. We present a case of heparin-induced fever in a patient who experienced a 32% total BSA friction burn after a motorcycle crash. [ABSTRACT FROM AUTHOR]